Chorea-predominant SCA5 mimicking Huntington's disease: A case report with a novel SPTBN2 variant

Chorea has diverse etiologies, with Huntington's disease (HD) being the most common genetic cause. While spinocerebellar ataxias (SCAs) rarely present with chorea, SCA5 is typically regarded as a "pure" cerebellar syndrome. To our knowledge, chorea has not been previously reported as the predominant manifestation of SCA5.

A 51-year-old male presented with progressive dysarthria and generalized chorea. Family history suggested autosomal dominant inheritance. Cranial MRI revealed cerebellar atrophy and frontal-horn enlargement. Initially misdiagnosed with HD, he received olanzapine, achieving partial relief. Whole-exome sequencing (WES) subsequently identified a novel heterozygous missense variant in SPTBN2(c.2531G > A, p.Arg844Gln), revising the diagnosis to SCA5. At the 9-month follow-up, chorea was significantly improved.

This case demonstrates that SPTBN2-related SCA5 can manifest as a chorea-predominant phenotype, easily misdiagnosed as HD. The identification of the novel c.2531G > A variant expands the phenotypic and mutational spectrum of SCA5. It underscores that WES should be considered early in autosomal dominant chorea with frontal-horn enlargement, particularly when cerebellar signs are subtle, to prevent diagnostic errors.